16-57628885-AGAGTGT-A

Position:

• chr16-57628885-AGAGTGT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_201525.4(ADGRG1):​c.-36+91_-36+96del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 122,282 control chromosomes in the GnomAD database, including 400 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (400 hom., cov: 29)
  • Exomes 𝑓: 0.020 (610 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.742

Genes affected

ADGRG1 (HGNC:4512): (adhesion G protein-coupled receptor G1) This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-57628885-AGAGTGT-A is Benign according to our data. Variant chr16-57628885-AGAGTGT-A is described in ClinVar as [Benign]. Clinvar id is 1296045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-36+91_-36+96del		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+91_-36+96del		intron_variant		1	NM_201525.4	P4
	ENST00000563251.1	n.273+1514_273+1519del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 7292 AN: 122174 Hom.: 397 Cov.: 29

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.00655

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.0407

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0299

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0556

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0202 AC: 13252 AN: 657396 Hom.: 610 AF XY: 0.0199 AC XY: 6053 AN XY: 304288

Gnomad4 AFR exome AF: 0.0831

Gnomad4 AMR exome AF: 0.0328

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.0791

Gnomad4 SAS exome AF: 0.0266

Gnomad4 FIN exome AF: 0.0121

Gnomad4 NFE exome AF: 0.0182

Gnomad4 OTH exome AF: 0.0268

GnomAD4 genome AF: 0.0599 AC: 7323 AN: 122282 Hom.: 400 Cov.: 29 AF XY: 0.0608 AC XY: 3662 AN XY: 60264

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0803

Gnomad4 ASJ AF: 0.00655

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.0405

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.0606

Alfa AF: 0.00739 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879267570; hg19: chr16-57662797;